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16-Mar-2019

Vedolizumab (Entyvio®) Achieves Superior Rates of Clinical Remission vs. Adalimumab (Humira®) in First Ever Head-to-Head Biologic Study in Ulcerative Colitis

−           Vedolizumab superior to adalimumab in achieving statistically significant clinical remission* (p=0.0061) and mucosal healing** (p=0.0005) at week 52 in patients with moderately to severely active ulcerative colitis

 

 

HIGH WYCOMBE, UK, March 11, 2019 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) has announced results from the Phase 3b head-to-head VARSITY study demonstrating vedolizumab (Entyvio®) was superior to adalimumab (Humira®) in achieving statistically significant (p=0.0061) clinical remission* in patients with moderately to severely active ulcerative colitis at week 52. Data showed 31.3% (n=120/383) of patients receiving intravenous (IV) vedolizumab achieved the primary endpoint of clinical remission compared to 22.5% (n=87/386) of patients treated with subcutaneous (SC) adalimumab at week 52. These results were announced on Saturday March 9, 2019, at the 14th Congress of the European Crohn’s and Colitis Organisation (ECCO) in Copenhagen, Denmark.[1]

 

Treatment with vedolizumab was also associated with significantly higher rates of mucosal healing** at week 52, compared to patients treated with adalimumab (39.7% vs 27.7%; p=0.0005). A non-significant difference in favour of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission*** at week 52. While the study was not powered to compare safety, over the 52 weeks, patients treated with vedolizumab had numerically lower rates of overall adverse events (62.7%) than patients treated with adalimumab (69.2%), infections (vedolizumab, 33.5%; adalimumab 43.5%) and serious adverse events (vedolizumab 11.0%; adalimumab 13.7%).1

 

“As the first biologic head-to-head trial in inflammatory bowel disease, VARSITY provides compelling data for the superiority of vedolizumab (Entyvio, an anti-integrin) in achieving clinical remission and mucosal healing over adalimumab, an anti-TNF therapy, in ulcerative colitis.” said Professor Simon Travis, Consultant Gastroenterologist at Oxford University Hospitals NHS Foundation Trust. “The goals of treatment for ulcerative colitis are to achieve clinical remission and mucosal healing. This landmark study raises the question of the optimal biologic for first-line therapy in patients with moderate to severely active ulcerative colitis and will challenge current practice.”

 

“As the first prospective clinical study to directly compare the efficacy and safety of two commonly used biologic therapies in patients with ulcerative colitis, VARSITY provides invaluable knowledge to help inform physicians’ treatment decisions when initiating biologic therapy,” said Jeff Bornstein, M.D., Executive Medical Director, Takeda. “This is also the first time we have seen a direct comparison between two medicines with distinct modes of action in ulcerative colitis, the gut-selective anti-alpha4beta7 integrin vedolizumab and the anti-TNFα adalimumab. This is an exciting time in the landscape of ulcerative colitis treatment, as head-to-head clinical data has not previously been available to guide treatment decisions around biologic therapies.”

 

VARSITY is a phase 3b, randomised, double-blind, double-dummy, multi-centre, active-controlled study to evaluate the efficacy and safety of vedolizumab IV compared to adalimumab SC at week 52 in patients with moderately to severely active ulcerative colitis. The study randomised 769 patients (vedolizumab n=383 or adalimumab n=386), all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or one TNFα-antagonist other than adalimumab prior to being enrolled. Patients were randomised into one of two treatment groups, vedolizumab IV and placebo SC or adalimumab SC and placebo IV. Patients in the vedolizumab group were administered vedolizumab IV 300 mg at weeks 0, 2, 6 and every 8 weeks thereafter until week 46, along with placebo SC at week 0 and every 2 weeks until week 50. The adalimumab group were administered adalimumab SC 160 mg at week 0, 80 mg at week 2 and 40 mg every 2 weeks until week 50, along with placebo IV at weeks 0, 2, 6 and every 8 weeks thereafter until week 46. Dose escalation was not permitted in either treatment arm during the study.1,[2]

 

* Primary endpoint: Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore ˃1 point.2

** Secondary endpoint: Mucosal healing is defined as Mayo endoscopic subscore of ≤1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis.2

*** Secondary endpoint: Corticosteroid-free clinical remission is defined as patients using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52.2

 

About Ulcerative Colitis

Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease (IBD).[3] UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal tract that is often progressive in nature, and involves the innermost lining of the large intestine.[4],[5] UC commonly presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus.5,[6] The cause of UC is not fully understood; however, recent research suggests hereditary, genetics, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to the condition.5,[7],[8]

 

About Entyvio® (vedolizumab)

Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.[9] It is a humanised monoclonal antibody designed to specifically antagonise the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1).[10] MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.[11] The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.10 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).10,[12],[13] By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.10

 

Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.9 Vedolizumab IV has been granted marketing authorisation in over 60 countries, including the United States and European Union, with more than 260,000 patient years of exposure to date.[14]

 

 

For UK audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.

 

Takeda’s Commitment to Gastroenterology

Gastrointestinal (GI) diseases can be complex, debilitating and life-changing. Recognising this unmet need, Takeda and our collaboration partners have focused on improving the lives of patients through the delivery of innovative medicines and dedicated patient disease support programs for over 25 years. Takeda aspires to advance how patients manage their disease.

 

About Takeda UK Ltd.

Takeda UK Ltd., located in High Wycombe, is the UK marketing and sales organisation of Takeda Pharmaceutical Company Limited, headquartered in Japan. Takeda Pharmaceutical Company Limited (TSE: 4502, NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.

 

Additional information about Takeda UK Ltd. is available through its corporate website, www.takeda.com/en-gb.

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Last Updated: 19-Mar-2019